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101.
Tannaza Batool Nasir Rasool Yasmeen Gull Mnaza Noreen Faiz-ul-Hassan Nasim Asma Yaqoob Muhammad Zubair Usman Ali Rana Salah Ud-Din Khan M. Zia-Ul-Haq Hawa Z. E. Jaafar 《PloS one》2014,9(12)
A highly convenient method has been developed for the synthesis of (prop-2-ynyloxy) benzene and its derivatives. Differently substituted phenol and aniline derivatives were allowed to react with propargyl bromide in the presence of K2CO3 base and acetone as solvent. The compounds were synthesized in good yields (53–85%). Low cost, high yields and easy availability of compounds helped in the synthesis. Electron withdrawing groups favor the formation of stable phenoxide ion thus in turn favors the formation of product while electron donating groups do not favor the reaction. Phenol derivatives gave good yields as compared to that of aniline. As aprotic polar solvents favor SN2 type reactions so acetone provided best solvation for the reactions. K2CO3 was proved to be good for the synthesis. Antibacterial, Antiurease and NO scavenging activity of synthesized compounds were also examined. 4-bromo-2-chloro-1-(prop-2-ynyloxy)benzene 2a was found most active compound against urease enzyme with a percentage inhibition of 82.00±0.09 at 100 µg/mL with IC50 value of 60.2. 2-bromo-4-methyl-1-(prop-2-ynyloxy)benzene 2d was found potent antibacterial against Bacillus subtillus showing excellent inhibitory action with percentage inhibition of 55.67±0.26 at 100 µg/ml wih IC50 value of 79.9. Based on results, it can be concluded that some of the synthesized compounds may have potential antiurease and antibacterial effects against several harmful substances. 相似文献
102.
NADPH: quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside: quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze reductive activation of carcinogens from cigarette smoke, such as nitrosamines and heterocyclic amines. These enzymes also protect cells against oxidative damage from reactive oxygen species. The present study investigated the associations of genetic variants of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to gastric cancer (GC) as well as their interactions with known risk factors in Kashmir valley. A case control study was performed in 303 subjects (108 GC and 195 healthy controls). All subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed by chi-square test and logistic regression model. The NQO1 609C>T TT genotype and T allele were significantly associated with increased risk for GC, whereas NQO2 -3423G>A polymorphism did not show any association with GC. Also, NQO1 609C>T TT genotype showed significant association with gastric adenocarcinoma. The interaction of NQO1/NQO2 genotypes with high consumption of salted tea, a known risk factor, did not further modulate the risk of GC. In conclusion, NQO1 609C>T polymorphism shows association with GC risk in Kashmir valley. 相似文献
103.
Yasmeen Rashid M. Kamran Azim Zafar S. Saify Khalid M. Khan Rasool Khan 《Bioorganic & medicinal chemistry letters》2012,22(19):6089-6094
The HslVU is the proteasome-related two component system composed of HslV peptidase and HslU chaperone. It is involved in the degradation of an array of intracellular proteins. The presence of HslVU homologs in pathogenic microbes and its absence in human makes it an antimicrobial drug target. The functional HslVU complex forms when HslV dodecamer is flanked at both ends by HslU hexamers. In the HslVU complex, eight residues at the carboxy termini of HslU subunits intercalate into a clefts between two adjacent HslV subunits causing a conformational change in the active site of HslV which in turn results in the allosteric activation of HslV peptidase. Here, we report small molecules capable of activating HslV peptidase in the absence of its natural activator HslU ATPase. For this purpose, virtual screening of an in-house library of synthetic and natural compounds was performed to find out ligands mimicking the interaction of HslU carboxy terminus with HslV dodecamer. The benzimidazole, quinazoline and chromone derivatives were suggested by ligand docking to bind at the HslU carboxy termini intercalation pockets in the HslV dodecamer. This was confirmed by HslV activation and isothermal titration calorimetry assays with these compounds that gave ED50 in sub-micromolar range (0.6–1.5 μM). The results showed for the first time that small, extracellular non-peptidic molecules can allosterically activate the peptide hydrolytic activity of HslV which in turn would initiate intracellular proteolysis. 相似文献
104.
S Rasool R Albay H Martinez-Coria L Breydo J Wu S Milton S Misra A Tran A Pensalfini F Laferla R Kayed C Glabe 《Molecular neurodegeneration》2012,7(1):37-14
ABSTRACT: BACKGROUND: It is well established that vaccination of humans and transgenic animals against fibrillar amyloid beta (Abeta) prevents amyloid accumulation in plaques and preserves cognitive function in transgenic mouse models. However, autoimmune side effects have halted the development of vaccines based on full length human Abeta. Further development of an effective vaccine depends on overcoming these side effects while maintaining an effective immune response. RESULTS: We have previously reported that the immune response to amyloid oligomers is largely directed against generic epitopes that are common to amyloid oligomers of many different proteins and independent of a specific amino acid sequence. Here we have examined whether we can exploit this generic immune response to develop a vaccine that targets amyloid oligomers using a non-human random sequence amyloid oligomer. In order to study the effect of vaccination against generic oligomer epitopes, a random sequence oligomer (3A) was selected as it forms oligomers that react with the oligomer specific A11 antibody. Oligomer mimics from 3A peptide, Abeta, islet amyloid polypeptide (IAPP), and Abeta fibrils were used to vaccinate Tg2576 mice, which develop a progressive accumulation of plaques and cognitive impairment. Vaccination with the 3A random sequence antigen was just as effective as vaccination with the other antigens in improving cognitive function and reducing total plaque load (Abeta burden) in the Tg2576 mouse brains. CONCLUSION: These results show that the amyloid Abeta sequence is not necessary to produce a protective immune response that specifically targets generic amyloid oligomers. Using a non-human, random sequence antigen may facilitate the development of a vaccine that avoids autoimmune side effects. 相似文献
105.
Muriel da Silva Folli-Pereira Lydice Sant’Anna Meira-Haddad Nazima Rasool Wagner Campos Otoni Maria Catarina Megumi Kasuya 《Plant biotechnology reports》2012,6(4):355-362
In this work, we attempted to assess the effects of inoculation of arbuscular mycorrhizal fungus (AMF), Glomus clarum, on the survival and development of micropropagated Jatropha curcas plantlets at different rooting stages. Elongated shoots (average 3?cm) of J. curcas, maintained for 0, 14, or 21?days on rooting medium in the presence or absence of 1?mg?L?1 indole-3-butyric acid (IBA), were transferred to a sand:soil:vermiculite (1:1/2:1) (v:v:v) substrate. At the time of transplantation, the plantlets were either inoculated or not inoculated with G. clarum that had been monoaxenically produced in Ri-transformed carrot roots. After a 2-week acclimatization period, 100?% of the plants kept for 0 or 14?days in rooting medium survived. However, those that remained for 21?days in rooting medium displayed post-acclimatization survival rates of 93 and 89?% for plants inoculated and non-inoculated with G. clarum, respectively. Colonization rates ranged from 70 to 93?%, and the stimulatory effects of AMF were evidenced by increased phosphorus uptake by plants and increases in all evaluated growth parameters, except plant height. Plants that were not subjected to the rooting stage showed growth similar to or higher than those subjected to the rooting stage, regardless of the addition of IBA. It can be concluded that stimulatory effects of mycorrhizal fungi were observed, and that the inoculation of J. curcas proved effective during the initial period of the acclimatization phase. 相似文献
106.
M. Sohail Haroone Rasool Baksh Tareen M. Ahmed Mesaik Saleem Jan Ahmed Abbaskhan Muhammad Asif Tahsin Gulzar Abdullah M. Al-Majid Sammer Yousuf M. Iqbal Choudhary 《Phytochemistry letters》2012,5(3):613-616
Two new compounds, (+)-3,5,7-trihydroxy-3-[3′-hydroxy-2′,4′-dimethoxy-5-(3-methyl-2-butenyl)]-phenyl-(3R)-4H-1-benzopyran-4-one (1) and (?)-3-hydroxy-8,9-methylenedioxy-(6aR,11aS)-pterocarpan (2), were isolated from the methanolic extract of Sophora mollis subsp. griffithii. Two known compounds, β-sitosterol (3) and 19βH-lupeol-methyl-ether (4), were also obtained for the first time from this plant. The structures of 1–4 were identified through their spectroscopic data. CD Spectroscopy was also utilized for the structure elucidation of compounds 1 and 2. Compounds 1, 3 and 4 were studied for their effects on immune cells and only 1 was found to be substantially active. 相似文献
107.
Samra Hafeez Mahwish Urooj Shamiala Saleem Zeeshan Gillani Sumaira Shaheen Mahmood Husain Qazi Muhammad Imran Naseer Zafar Iqbal Shakeel Ahmed Ansari Absarul Haque Muhammad Asif Manzoor Ahmad Mir Ashraf Ali Peter Natesan Pushparaj Mohammad Sarwar Jamal Mahmood Rasool 《PloS one》2016,11(1)
This study has been undertaken to explore the therapeutic effects of deguelin and specific siRNAs in HeLa cells. The data provided clearly show the silencing of ERK 1/2 with siRNAs and inhibition of ERK1/2 with deguelin treatment in HeLa cells. Additionally, we are providing information that deguelin binds directly to anti-apoptotic Bcl-2, Bcl-xl and Mcl-1 in the hydrophobic grooves, thereby releasing BAD and BAX from dimerization with these proteins. This results in increased apoptotic activity through the intrinsic pathway involved in rupture of mitochondrial membrane and release of cytochrome C. Evidence for inhibition of ERK1/2 by deguelin and escape of BAD phosphorylation at serine 112 through ERK/RSK pathway has been further fortified by obtaining similar results by silencing ERK 1/2 each with specific siRNAs. Increase in BAD after treatment with deguelin or siRNAs has been interpreted to mean that deguelin acts through several alternative pathways and therefore can be used as effective therapeutic agent. 相似文献
108.
Sadia Saeed Sheikh Ajaz Rasool Samia Ahmed Tanweer Khanum Muhammad Bashir Khan Atiya Abbasi Syed Abid Ali 《World journal of microbiology & biotechnology》2006,22(7):713-722
Summary
Staphylococcus aureus AB188 (a clinical isolate from wound pus) has been found to produce bacteriocins and/or bacteriocin-like inhibitory substance(s)
tentatively termed staphylococcin Bac188. It has a broad activity spectrum against many Gram-positive (e.g. B. subtilis, S. aureus, E. faecalis), Gram-negative bacteria (e.g. E. coli, S. typhi and S. dysenteriae), and dermatophytes including Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton longi and Trichophyton rubrum. Interestingly, staphylococcin Bac188 also showed very potent activity against many clinical isolates of Mycobacterium tuberculosis. Staphylococcin Bac188 showed wide thermostability and remained stable over the wide pH range (pH 2–14). It was also resistant
to treatment with chloroform, catalase, lipase and lysozyme, but showed sensitivity to proteinase K, trypsin and α-chymotrypsin suggesting its proteinaceous nature. Staphylococcin Bac188 revealed bactericidal effects on the S. aureus SS-1 sensitive strain as well as on E. coli and S. typhi, suggesting a similar mode of action on both Gram-negative and Gram-positive organisms. The antimicrobial, antidermatophytic
and antimycobacterial activities expressed by S. aureus AB188 correlate with the production of a bacteriocin and/or bacteriocin-like inhibitory substance with properties similar
to other staphylococcins reported earlier. To our knowledge, this is the first report describing such wide possible clinical
applications of a bacteriocin and/or bacteriocin-like inhibitory substance produced by S. aureus AB188, suggesting further investigation for potential therapeutic development. 相似文献
109.
Varthakavi V Heimann-Nichols E Smith RM Sun Y Bram RJ Ali S Rose J Ding L Spearman P 《Nature medicine》2008,14(6):641-647
The HIV-1 Vpu protein is required for efficient viral release from human cells. For HIV-2, the envelope (Env) protein replaces the role of Vpu. Both Vpu and HIV-2 Env enhance virus release by counteracting an innate host-cell block within human cells that is absent in African green monkey (AGM) cells. Here we identify calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting host factor that restricts HIV-1 release. Expression of human CAML (encoded by CAMLG) in AGM cells conferred a strong restriction of virus release that was reversed by Vpu and HIV-2 Env, suggesting that CAML is the mechanistic link between these two viral regulators. Depletion of CAML in human cells eliminated the need for Vpu in enhancing HIV-1 and murine leukemia virus release. These results point to CAML as a Vpu-sensitive host restriction factor that inhibits HIV release from human cells. The ability of CAML to inhibit virus release should illuminate new therapeutic strategies against HIV. 相似文献
110.